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BACKGROUND: SARS-CoV-2 variants evade immunity despite vaccination with prototype COVID-19 vaccines or previous infection. The 2019nCoV-311 (part 2) study is evaluating immune responses after two booster doses of a vaccine containing the omicron BA.5 subvariant spike protein in adults previously vaccinated with a prototype mRNA vaccine. This interim analysis reports on day 28 immunogenicity and safety outcomes after one booster dose. METHODS: In this phase 3, randomised, observer-blinded study conducted at 35 sites in Australia, medically stable, previously COVID-19-vaccinated (mRNA-based; ≥three doses) adults aged 18 years or older were enrolled and randomly allocated (1:1:1; via an interactive web response system) to receive two doses of bivalent (NVX-CoV2373 + NVX-CoV2540; bivalent group), authorised prototype (NVX-CoV2373; prototype group), or BA.5 (NVX-CoV2540; BA.5 group) vaccine. Only blinded personnel performed study assessments or had participant contact to collect data after study vaccination. Participants received vaccines containing 5 µg SARS-CoV-2 recombinant spike protein and 50 µg Matrix-M adjuvant, administered via a 0·5 mL intramuscular injection (2·5 µg of NVX-CoV2373 plus 2·5 µg of NVX-CoV2540 for the bivalent vaccine, prepared on-site as a 1:1 mixture). The coprimary endpoints include day 28 neutralising antibody geometric mean titre (GMT) ratios (GMTRs) to omicron BA.5 and the ancestral strain, and seroresponse rates to BA.5, in the bivalent and prototype groups. These endpoints were calculated in the per-protocol analysis set, which was defined as participants who had received a vaccine dose, had baseline and day 28 immunogenicity data, and were PCR-negative for SARS-CoV-2, with no major protocol deviations. The primary objective was to determine the primary outcome (antibody responses), which consisted of three comparisons: superiority of the bivalent versus prototype vaccine for neutralising antibody GMT to BA.5 (ie, lower bound of the GMTR 95% CI >1·0); non-inferiority of neutralising antibody seroresponse rate to BA.5 (ie, lower bound of the seroresponse rate 95% CI >-5%); and non-inferiority of neutralising antibody GMT to the ancestral strain (ie, lower bound of GMTR 95% CI >0·67). This trial was registered at ClinicalTrials.gov, number NCT05372588. FINDINGS: Between March 22, 2023 and May 2, 2023, 837 participants were screened for eligibility and 766 were randomly allocated to receive the BA.5 (n=255), prototype (n=252), or bivalent (n=259) vaccine. After accounting for exclusions due to participants being baseline SARS-CoV-2-positive, having previous infection, or protocol deviations, the per-protocol analysis set included 694 participants (236 in BA.5 group, 227 in prototype group, and 231 in bivalent group). In this interim analysis (maximum follow-up 35 days after the first dose), the bivalent group, compared with the prototype group, had superior neutralising antibody responses to BA.5 (GMT 1017·8 [95% CI 891·0-1162·6] vs 515·1 [450·4-589·0]; GMTR 2·0 [1·69-2·33]) and a non-inferior seroresponse rate to BA.5 at day 28 (39·8% [33·5-46·5] vs 12·3% [8·4-17·3]; difference 27·5% [19·8-35·0]). The bivalent group also had non-inferior neutralising antibody responses to the ancestral strain (GMTR 1·0 [0·84-1·20]), compared with the prototype group. All vaccines were similarly well tolerated. INTERPRETATION: All three coprimary endpoints were met in part 2 of the ongoing 2019nCoV-311 study. These data support the development of monovalent and/or bivalent vaccines for the most currently circulating variants, to optimise protection. With no new safety findings, further investigation of omicron-based subvariant vaccines is supported by the evidence. FUNDING: Novavax.
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Anticuerpos Neutralizantes , Anticuerpos Antivirales , Vacunas contra la COVID-19 , COVID-19 , Inmunización Secundaria , Inmunogenicidad Vacunal , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Humanos , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Glicoproteína de la Espiga del Coronavirus/inmunología , Masculino , COVID-19/prevención & control , COVID-19/inmunología , SARS-CoV-2/inmunología , Femenino , Inmunización Secundaria/métodos , Persona de Mediana Edad , Adulto , Anticuerpos Antivirales/sangre , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Vacunas Sintéticas/inmunología , Vacunas Sintéticas/administración & dosificación , Anciano , Australia , Adulto JovenRESUMEN
The vast majority of excitatory synapses are formed on small dendritic protrusions termed dendritic spines. Dendritic spines vary in size and density that are crucial determinants of excitatory synaptic transmission. Aberrations in spine morphogenesis can compromise brain function and have been associated with neuropsychiatric disorders. Actin filaments (F-actin) are the major structural component of dendritic spines, and therefore, actin-binding proteins (ABP) that control F-actin dis-/assembly moved into the focus as critical regulators of brain function. Studies of the past decade identified the ABP cofilin1 as a key regulator of spine morphology, synaptic transmission, and behavior, and they emphasized the necessity for a tight control of cofilin1 to ensure proper brain function. Here, we report spine enrichment of cyclase-associated protein 1 (CAP1), a conserved multidomain protein with largely unknown physiological functions. Super-resolution microscopy and live cell imaging of CAP1-deficient hippocampal neurons revealed impaired synaptic F-actin organization and dynamics associated with alterations in spine morphology. Mechanistically, we found that CAP1 cooperates with cofilin1 in spines and that its helical folded domain is relevant for this interaction. Moreover, our data proved functional interdependence of CAP1 and cofilin1 in control of spine morphology. In summary, we identified CAP1 as a novel regulator of the postsynaptic actin cytoskeleton that is essential for synaptic cofilin1 activity.
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Actinas , Espinas Dendríticas , Actinas/metabolismo , Espinas Dendríticas/fisiología , Citoesqueleto de Actina/metabolismo , Sinapsis/metabolismo , Proteínas de Microfilamentos/genética , Proteínas de Microfilamentos/metabolismo , Sinapsinas/metabolismoRESUMEN
Many public opinion surveys compare trust in a number of different information and (mediated) knowledge sources, typically using closed questions with a set of answer categories that are imposed by researchers. We aim to validate these categories by quantitatively comparing survey responses about trustworthy sources using open and closed questions, and by qualitatively analyzing the open answers. The results show that answer options typically used for closed questions in academic research are generally valid and closely match categories that respondents come up with unprimed. In some cases, answers to open questions can be non-exhaustive, particularly when sources are considered trustworthy but are not salient for respondents. Open questions, however, may still be useful for exploratory research or more detailed investigations of media diets on the outlet-level. Qualitative approaches to open questions can also give more insight into motivations for distrust, e.g. perceptions of inconsistency or a fundamental rejection of the shared factual basis of an issue. In addition, our results indicate that respondents' interpretation of answer categories may change reported levels of trust: those that think of more specific outlets tend to report higher general media trust. This study provides new insights into how question design, and particularly the choice of answer options, may influence reported levels and sources of trust, and how qualitative and quantitative approaches to trust measurement can be combined.
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(Reprinted with permission from Br J Psychiatry 2005; 207: 235-242).
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BACKGROUND: Growing concerns regarding the adverse effects of antibiotics during the first days of life and the marked reduction in the incidence of early-onset sepsis (EOS) are changing the clinical practice for managing neonates at risk of EOS. Strategies avoiding unnecessary antibiotics while promoting mother-infant bonding and breastfeeding deserve to be considered. MAIN BODY: We compare strategies for managing newborns at risk of EOS recommended by the American Academy of Pediatrics, which are among the most followed recommendations worldwide. Currently three different approaches are suggested in asymptomatic full-term or late preterm neonates: i) the conventional management, based on standard perinatal risk factors for EOS alone, ii) the neonatal sepsis calculator, a multivariate risk assessment based on individualized, quantitative risk estimates (relying on maternal risk factors for EOS) combined with physical examination findings at birth and in the following hours and iii) an approach entirely based on newborn clinical condition (serial clinical observation) during the first 48 h of life. We discuss advantages and limitations of these approaches, by analyzing studies supporting each strategy. Approximately 40% of infants who develop EOS cannot be identified on the basis of maternal RFs or laboratory tests, therefore close monitoring of the asymptomatic but at-risk infant remains crucial. A key question is to know what proportion of babies with mild, unspecific symptoms at birth can be managed safely without giving antibiotics. CONCLUSIONS: Both neonatal sepsis calculator and serial clinical observation may miss cases of EOS, and clinical vigilance for all neonates is essential There is a need to assess which symptoms at birth are more predictive of EOS, and therefore require immediate interventions, or symptoms that can be carefully reevaluated without necessarily treat immediately the neonate with antibiotics. Studies comparing strategies for managing neonates are recommended.
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Sepsis Neonatal/diagnóstico , Sepsis Neonatal/tratamiento farmacológico , Antibacterianos/uso terapéutico , Diagnóstico Diferencial , Humanos , Recién Nacido , Examen Físico , Medición de RiesgoRESUMEN
BACKGROUND: In Italy, leprosy diagnosis is reported in immigrants from endemic countries or Italians who have stayed in endemic areas. We report the first leprosy case to be observed in a migrant from Nigeria in the Rimini district (Emilia-Romagna, Northern Italy). METHODS: After describing the tasks of the various health Institutions in the Italian integrated system for diagnosis, treatment, and surveillance of leprosy, we describe the management and outcomes of the leprosy case and of the patient's contacts. RESULTS: In April 2017, Multibacillary Lepromatose Leprosy was diagnosed in a 29-year-old Nigerian man who arrived in Rimini in July 2014 after a 2-year stay in Libya. The local Public Health Service implemented the epidemiological investigation and identified the patient's close contacts. The management of the case and the surveillance of the 13 identified contacts, 7 Italians and 6 migrants, highlighted some critical issues. The late diagnosis of the case, due to the lack of knowledge of exotic diseases by general practitioners and other health and social professionals, and the loss at follow up of the close contacts (5 out of 6 migrants), represented important obstacles to the full success of surveillance measures. CONCLUSIONS: Although in Italy there is a well codified system of notification and surveillance of leprosy, the recognising of cases and the tracing and follow up of contacts are made difficult by the particular conditions of the involved people. This represents a new challenge for the Italian Public Health Authorities which, in the current context of immigration, often uncontrolled, must know how to respond to the new needs, in close collaboration with the State Institutions responsible for registering migrants and those health and social professionals who could facilitate the access of foreign people to health services.
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Trazado de Contacto , Lepra/diagnóstico , Migrantes , Adulto , Diagnóstico Tardío , Notificación de Enfermedades , Humanos , Italia , Lepra/terapia , Masculino , Nigeria/etnología , Vigilancia de la Población/métodos , Salud PúblicaRESUMEN
BACKGROUND: Chronic inflammatory vulvar diseases can have a huge detrimental impact on patient welfare. A few studies have addressed this issue so far, mainly measuring patients' quality of life or sexual dysfunction. OBJECTIVE: To assess the burden of suffering in patients with chronic inflammatory vulvar diseases using the Pictorial Representation of Illness and Self-Measure (PRISM), a visual, non-verbal instrument. We also assessed (i) the concordance between PRISM and the Dermatology Life Quality Index (DLQI), (ii) whether some variables, both patient-related and disease-related, affect the patient's suffering and quality-of-life impairment. METHODS: We evaluated for inclusion in this cross-sectional study all patients who attended our Vulva Unit over a 9-month period with histologically proven lichen sclerosus (LS), lichen planus (LP), lichen simplex chronicus (LSC), eczema, plasma cell vulvitis and psoriasis (at least five for each disease). Demographics and disease-related subjective and objective scores were recorded. The PRISM and DLQI were administered. RESULTS: We included 87 patients affected with LS, 13 with LSC and seven with LP. Median PRISM values (0-273 mm) ranged from 95 to 120 mm, depending on the disease, and median DLQI scores (0-30) were five for all three groups. Neither PRISM nor DLQI scores differed significantly among the three groups. Moderate coherence was found between PRISM and DLQI (ρ = 0.5455, P < 0.001). Global subjective score was the only variable significantly associated with the degree of suffering and quality-of-life impairment. CONCLUSIONS: Pictorial Representation of Illness and Self-Measure proved to be a valuable, highly reliable tool for measuring the perceived burden in these patients. In spite of a moderate correlation, PRISM resulted more sensitive in capturing patient distress than DLQI.
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Calidad de Vida , Enfermedades de la Vulva , Estudios Transversales , Femenino , Humanos , Índice de Severidad de la Enfermedad , Encuestas y CuestionariosAsunto(s)
Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Mediadores de Inflamación/metabolismo , Inestabilidad de Microsatélites , Antineoplásicos/administración & dosificación , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Reparación de la Incompatibilidad de ADN/efectos de los fármacos , Reparación de la Incompatibilidad de ADN/fisiología , Pruebas Genéticas/métodos , Humanos , Mediadores de Inflamación/antagonistas & inhibidores , Inestabilidad de Microsatélites/efectos de los fármacos , Valor Predictivo de las PruebasRESUMEN
An increasing lack of information truthfulness has become a fundamental challenge to communications. Insights into how to debunk this type of misinformation can especially be crucial for public health crises. To identify corrective information strategies that increase awareness and trigger actions during infectious disease outbreaks, an online experiment (N = 700) was conducted, using a U.S. sample. After initial misinformation exposure, participants' exposure to corrective information type (simple rebuttal vs. factual elaboration) and source (government health agency vs. news media vs. social peer) was varied, including a control group without corrective information. Results show that, if corrective information is present rather than absent, incorrect beliefs based on misinformation are debunked and the exposure to factual elaboration, compared to simple rebuttal, stimulates intentions to take protective actions. Moreover, government agency and news media sources are found to be more successful in improving belief accuracy compared to social peers. The observed mediating role of crisis emotions reveals the mechanism underlying the effects of corrective information. The findings contribute to misinformation research by providing a formula for correcting the increasing spread of misinformation in times of crisis.
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Comunicación , Brotes de Enfermedades , Salud Pública , Agencias Gubernamentales , Humanos , Medios de Comunicación de Masas , Medios de Comunicación SocialesRESUMEN
Photocatalysis is a promising method to harness solar energy and use it to form fuels and other high-value chemicals, but most sensitizers used in photocatalytic reactions are complexes of rare and expensive metals such as ruthenium and iridium. Zinc dipyrromethene complexes have potential to be a more earth-abundant alternative, but their photophysical properties are largely unexplored. In this study, triplet state formation was quantified in two zinc dipyrromethene complexes, with and without heavy atoms, by transient absorption spectroscopy. Without heavy atoms, the triplet quantum yield was 16% in toluene and 27% in THF. With the addition of heavy I atoms, the triplet quantum yield increased to 62-63% and was insensitive to solvent polarity. The fact that in the absence of heavy atoms the triplet yield is affected by solvent polarity and in the presence of heavy atoms it is not suggests that triplet formation occurs through different pathways in the two complexes. These triplet yields meet or exceed those of successful organic photosensitizers, illustrating the potential for zinc dipyrromethene complexes as photosensitizers.
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Dermatitis Alérgica por Contacto/diagnóstico , Dermatitis Irritante/diagnóstico , Dermoscopía , Piel/diagnóstico por imagen , Adulto , Estudios Transversales , Diagnóstico Diferencial , Estudios de Factibilidad , Femenino , Humanos , Irritantes/administración & dosificación , Masculino , Pruebas del Parche , Proyectos Piloto , Piel/efectos de los fármacosRESUMEN
BACKGROUND: According to the current guidelines, the aim of vulvar lichen sclerosus (VLS) treatment was to improve symptoms and signs, not to cure. OBJECTIVE: To assess (i) the rate of patients with VLS who achieved complete clearance of symptoms or objective features, or both, with a 12-week pharmacological treatment and (ii) the predictive value of therapeutic response to the demographic and clinical features. METHODS: We retrospectively included patients with VLS who had undergone any topical treatment for 12 weeks; demographics, history, VLS-related symptoms and objective features recorded at baseline and on completion of treatment were collected and elaborated. The primary study endpoint was to assess the rate of patients achieving complete clearance of global subjective score (GSS), or in global objective score (GOS), and in both scores. RESULTS: One hundred and ninety-six patients were included; 24 (12.2%) were asymptomatic at baseline, and nine (4.6%) dropped out. After treatment, 78 patients (47.3%) achieved GSS = 0, 40 (21.4%) achieved GOS = 0, and 23 (13.9%) achieved complete clearance of both symptoms and signs. Lower symptom scores at baseline and shorter disease duration were associated with the achievement of symptom clearance at the end of the treatment. Earlier disease onset, diagnosis and beginning of study treatment as well as lower baseline GOS were significantly associated with complete recovery of VLS signs and clearance of both symptoms and signs. CONCLUSION: A relevant part of patients who undergo a 12-week topical treatment is not completely cured of VLS. It may be hypothesized that these patients, in spite of a significant improvement, may still have substantial residual disease and, as a result, its effect on their quality of life.
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Liquen Escleroso Vulvar/diagnóstico , Liquen Escleroso Vulvar/tratamiento farmacológico , Adolescente , Adulto , Edad de Inicio , Anciano , Anciano de 80 o más Años , Dispareunia/etiología , Diagnóstico Precoz , Femenino , Humanos , Persona de Mediana Edad , Dolor/etiología , Prurito/etiología , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Evaluación de Síntomas , Resultado del Tratamiento , Adulto JovenAsunto(s)
Quemaduras/etiología , Teléfono Celular , Suministros de Energía Eléctrica , Adulto , Explosiones , Femenino , Humanos , Litio , MusloRESUMEN
As gatekeepers, journalists have the power to select the sources that get a voice in crisis coverage. The aim of this study is to find out how journalists select sources during a crisis. In a survey, journalists were asked how they assess the following sources during an organizational crisis: news agencies, an organization undergoing a crisis, and the general public. The sample consisted of 214 Dutch experienced journalists who at least once covered a crisis. Using structural equation modeling, sources' likelihood of being included in the news was predicted using five source characteristics: credibility, knowledge, willingness, timeliness, and the relationship with the journalist. Findings indicated that during a crisis, news agencies are most likely to be included in the news, followed by the public, and finally the organization. The significance of the five source characteristics is dependent on source type. For example, to be used in the news, news agencies and organizations should be mainly evaluated as knowledgeable, whereas information from the public should be both credible and timely. In addition, organizations should not be seen as too willing or too eager to communicate. The findings imply that, during a crisis, journalists remain critical gatekeepers; however, they rely mainly on familiar sources.
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A major concern during pesticide development and use is the impact on non-target species, such as raptors or domestic cats and dogs. Sodium nitrite and para-aminopropiophenone (PAPP) are two toxicants currently being studied for the control of invasive species, such as starlings and feral swine. When given to an animal these compounds oxidize hemoglobin, which renders it unable to carry oxygen resulting in methemoglobinemia. This study developed a method to estimate methemoglobin levels in mammals and birds by examining the efficacy of sodium nitrite to induce the conversion of hemoglobin to methemoglobin. Varying concentrations of sodium nitrite were added to aliquots of coyote, vole, feral swine, starling, and duck blood, collected from captive animals. The blood samples were analyzed spectrophotometrically to determine percent methemoglobin and digitally to determine red color values (RCV) associated with different methemoglobin levels. The avian and mammalian blood reached 100% methemoglobin levels at 200 mM and 15 mM sodium nitrite, respectively. All animals had similar RCV for a given percent methemoglobin. In conclusion, this study developed a procedure to quickly determine methemoglobin levels in mammals and birds. Furthermore, percent methemoglobin can be estimated with one standard curve from any animal species and an image of a blood spot. The technique will be useful during field studies, in agricultural areas, or in a veterinarian's office for the rapid diagnosis of methemoglobinemia in non-target animals that have eaten toxicants/baits or baited animals.
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Animales Salvajes/sangre , Metahemoglobinemia/veterinaria , Animales , Arvicolinae/sangre , Enfermedades de las Aves/sangre , Enfermedades de las Aves/diagnóstico , Colorimetría/veterinaria , Coyotes/sangre , Patos/sangre , Metahemoglobina/análisis , Metahemoglobina/efectos de los fármacos , Metahemoglobinemia/sangre , Metahemoglobinemia/diagnóstico , Nitrito de Sodio/farmacología , Espectrofotometría/veterinaria , Estorninos/sangre , Porcinos/sangre , Enfermedades de los Porcinos/sangre , Enfermedades de los Porcinos/diagnósticoRESUMEN
BACKGROUND: Twice-weekly proactive application of mometasone furoate 0.1% ointment (MMF) over 52 weeks was found to be an effective and safe therapy option in maintaining vulvar lichen sclerosus (VLS) remission and in preventing relapse. OBJECTIVE: To assess and compare the effectiveness and safety of two different topical corticosteroids, clobetasol propionate 0.05% ointment (CP) and MMF, administered twice weekly as a maintenance therapy of VLS previously stabilized with a topical corticosteroid course. METHODS: Forty-eight patients affected with VLS who had responded to therapy with either CP or MMF in an earlier 12-week randomized active treatment phase trial were enroled in a 52-week maintenance phase (MP) to apply their previous treatment twice weekly. The main efficacy parameters were the relapse rate, the mean time of relapse, and the change in symptom and sign severity throughout MP. RESULTS: By the end of the 52-week MP, 2 (8.33%) subjects among the CP patients and 1 (4.17%) among the MMF patients experienced a relapse; among relapsing patients the mean time to relapse was 30 weeks. Neither subjective nor objective scores changed significantly during MP among CP and MMF patients. No significant differences were found in any of the assessed efficacy endpoints between CP and MMF. Both treatments were well tolerated and the proactive regimen was judged as convenient by patients. CONCLUSIONS: Proactive application of the ultra-potent CP and the potent MMF was found to be an effective, safe and suitable maintenance treatment for long-term management of VLS. There were no differences between the two corticosteroids.